Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication

Raduà, Joaquim; Borgwardt, Stefan; Crescini, Alessandra; Mataix‐Cols, David; Meyer‐Lindenberg, Andreas; McGuire, Philip; Fusar‐Poli, Paolo

doi:10.1016/j.neubiorev.2012.07.012

Cited by 299 publications

(253 citation statements)

References 51 publications

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“…Given the association with schizophrenia, we focused our attention on regions defined by a recent meta-analysis of first-episode psychosis 21 (Fig. 3a).…”

Section: Structural Mri Phenotypesmentioning

confidence: 99%

“…Additional region-of-interest (ROI) analyses were performed in the following regions found to show both functional and structural abnormalities in a recent meta-analysis of subjects with high risk of schizophrenia 21 : anterior cingulate and medial frontal cortex, and bilateral insula extending into temporal and parietal cortex. Results of these ROI analysis were considered significant at P , 0.05 voxel level, FWE-corrected.…”

Section: Article Researchmentioning

confidence: 99%

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CNVs conferring risk of autism or schizophrenia affect cognition in controls

Stefánsson

Meyer‐Lindenberg

Steinberg

et al. 2013

Nature

612

568

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In a small fraction of patients with schizophrenia or autism, alleles of copy-number variants (CNVs) in their genomes are probably the strongest factors contributing to the pathogenesis of the disease. These CNVs may provide an entry point for investigations into the mechanisms of brain function and dysfunction alike. They are not fully penetrant and offer an opportunity to study their effects separate from that of manifest disease. Here we show in an Icelandic sample that a few of the CNVs clearly alter fecundity (measured as the number of children by age 45). Furthermore, we use various tests of cognitive function to demonstrate that control subjects carrying the CNVs perform at a level that is between that of schizophrenia patients and population controls. The CNVs do not all affect the same cognitive domains, hence the cognitive deficits that drive or accompany the pathogenesis vary from one CNV to another. Controls carrying the chromosome 15q11.2 deletion between breakpoints 1 and 2 (15q11.2(BP1-BP2) deletion) have a history of dyslexia and dyscalculia, even after adjusting for IQ in the analysis, and the CNVonly confers modest effects on other cognitive traits. The 15q11.2(BP1-BP2) deletion affects brain structure in a pattern consistent with both that observed during first-episode psychosis in schizophrenia and that of structural correlates in dyslexia.Little information is available on whether or how rare CNVs conferring high risk of schizophrenia and/or autism affect physiologic function of otherwise normal brains. As none of these CNVs hitherto described are fully penetrant for the diseases, and both schizophrenia and autism affect cognition, we aimed to examine the possibility that the CNVs affect cognition in control carriers, those who do not suffer either disease or intellectual disability. We based our selection of CNVs on a literature search for CNVs associated with schizophrenia and/or autism ('neuropsychiatric CNVs'); this search produced 26 CNV alleles (Supplementary Table 1) 1-3 . These CNV alleles are rare, found in 0.002% to 0.2% frequency, and cumulatively in 1.16% of our sample of 101,655 genotyped subjects, representing approximately one-third of the Icelandic population ( Supplementary Tables 1 and 2).We used the subset of genotyped subjects born before 1968, without excluding patients, to examine the association of each neuropsychiatric CNV with reproductive outcome ('fecundity'), defined simply as the number of children each subject had by age 45. After correction for multiple comparisons, three neuropsychiatric CNVs were significantly associated with fecundity (Table 1). Subjects carrying the 16p11.2 deletion or the 22q11.21 duplication show reduced fecundity, with the effect in males significantly greater than in females (P 5 0.0083 and P 5 0.029 for the difference in effect by sex for the 16p11.2 deletion and the 22q11.21 duplication, respectively). In contrast, individuals carrying the 16p12.1 deletion have more children than do controls (Table 1). Those with deletions at 15q11.2(...

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“…Given the association with schizophrenia, we focused our attention on regions defined by a recent meta-analysis of first-episode psychosis 21 (Fig. 3a).…”

Section: Structural Mri Phenotypesmentioning

confidence: 99%

Section: Article Researchmentioning

confidence: 99%

CNVs conferring risk of autism or schizophrenia affect cognition in controls

Stefánsson

Meyer‐Lindenberg

Steinberg

et al. 2013

Nature

612

568

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“…In two recent meta-analyses of voxel-based volumetric studies in FEP, STG and insular volume loss were identified (Fusar-Poli et al, 2011b;Radua et al, 2012). Others identified right (Witthaus et al, 2009) and bilateral (Takahashi et al, 2010) STG reduction in individuals at ultra-high risk of psychosis (UHR), and a recent meta-analysis associated STG volume reduction with transition from UHR to psychosis (Fusar-Poli et al, 2011a).…”

Section: Cerebral Cortexmentioning

confidence: 99%

Cortical thinning and caudate abnormalities in first episode psychosis and their association with clinical outcome

Scanlon

Anderson‐Schmidt

Kilmartin

et al. 2014

Schizophrenia Research

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First episode psychosis (FEP) has been associated with structural brain changes, largely identified by volumetric analyses. Advances in neuroimaging processing have made it possible to measure geometric properties that may identify subtle structural changes not appreciated by a measure of volume alone. In this study we adopt complementary methods of assessing the structural integrity of grey matter in FEP patients and assess whether these relate to patient clinical and functional outcome at 3 year follow-up. 1.5 Tesla T1-weighted Magnetic Resonance (MR) images were acquired for 46 patients experiencing their first episode of psychosis and 46 healthy controls. Cerebral cortical thickness and local gyrification index (LGI) were investigated using FreeSurfer software. Volume and shape of the hippocampus, caudate and lateral ventricles were assessed using manual tracing and spherical harmonics applied for shape description. A cluster of cortical thinning was identified in FEP compared to controls; this was located in the right superior temporal gyrus, sulcus, extended into the middle temporal gyrus (lateral temporal cortex -LTC). Bilateral caudate volumes were significantly lower in FEP relative to controls and the right caudate also displayed regions of shape deflation in the FEP group. No significant structural abnormalities were identified in cortical LGI or hippocampal or lateral ventricle volume/shape. Neither LTC nor caudate abnormalities were related to change in symptom severity or global functioning 3 years later. LTC and caudate abnormalities are present at the first episode of psychosis but do not appear to directly affect clinical or functional outcome.

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“…To examine the effects of age on GMV abnormalities in BPD, a meta-regression was conducted using a more conservative voxel-level threshold of p ≤ 0.0005 (uncorrected) in accordance with previous meta-analyses (Hart et al, 2012;Radua et al, 2012a;Lim et al, 2014). In line with this conservative approach, we decided to use a cluster-level extent threshold of k ≥ 20.…”

Section: Study Criteria and Data Extractionmentioning

confidence: 99%

Age-related parieto-occipital and other gray matter changes in borderline personality disorder: A meta-analysis of cortical and subcortical structures

Kimmel

Alhassoon

Wollman

et al. 2016

Psychiatry Research: Neuroimaging

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Previous research suggests that core borderline personality disorder (BPD) symptoms increase or decrease in severity with advancing age. While structural neuroimaging studies show smaller limbic and prefrontal gray matter volumes (GMV) in primarily adult and adolescent BPD patients, respectively, findings are inconsistent. Using the effect-size signed differential mapping (ES-SDM) meta-analytic method, we investigated the relationship between advancing age and GMV abnormalities in BPD patients. A total of nine voxel-based morphometry (VBM) studies comparing regional GMV of 256 BPD patients and 272 healthy control subjects were included.Meta-analysis identified lower GMV in the right superior/middle temporal gyri and higher GMV in the right supplementary motor area of BPD patients. Meta-regression showed that increasing Age-Related Gray Matter Changes in Borderline Personality 2 age was significantly associated with increased GMV in the left superior parieto-occipital gyri, with younger-aged patients starting at lower GMV compared to controls. In contrast, increasing age was associated with decreased GMV in the right amygdala. These findings suggest that while GMV deficits in limbic structures may become pronounced with advancing age in the course of BPD, parieto-occipital rather than frontal GMV deficits could be especially prominent in younger-aged BPD patients.

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Multimodal meta-analysis of structural and functional brain changes in first episode psychosis and the effects of antipsychotic medication

Cited by 299 publications

References 51 publications

CNVs conferring risk of autism or schizophrenia affect cognition in controls

CNVs conferring risk of autism or schizophrenia affect cognition in controls

Cortical thinning and caudate abnormalities in first episode psychosis and their association with clinical outcome

Age-related parieto-occipital and other gray matter changes in borderline personality disorder: A meta-analysis of cortical and subcortical structures

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